Prenatal DiagnosisNCT07606989
Utility of Whole Genome Sequencing in Fetuses With Abnormal Ultrasound Findings
An observational study of Prenatal Diagnosis and Fetal Diseases, run by Women's Hospital School Of Medicine Zhejiang University at 4 sites in China.
Trial summary
The goal of this observational study is to learn if whole-genome sequencing (WGS) can help find the genetic cause in fetuses with structural abnormalities that remain unexplained after standard genetic testing (such as karyotyping, chromosomal microarray, or whole-exome sequencing). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Prenatal Diagnosis, Fetal Diseases
- How many people
- 1,000 participants
- Where
- 4 sitesChina
- Study dates
- 12 Mar 2026to 12 Mar 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Pregnant women aged 18 years or older with singleton pregnancies, whose fetuses have structural abnormalities detected by ultrasound or MRI between 11+0 and 32+0 weeks of gestation, and who are scheduled to undergo invasive or postnatal genetic diagnostic procedures.
Who may be able to join
- Pregnant women aged ≥ 18 years.
- Singleton pregnancy.
- Gestational age between 11+0 and 32+0 weeks, with ultrasound or MRI indicating a definite structural malformation in the fetus (may be with or without soft marker abnormalities) requiring prenatal diagnosis (see Appendices 1 and 2). Fetal developmental abnormalities include those of the central nervous system, cardiovascular system, craniofacial/neck region, chest/mediastinum, abdomen/digestive tract, urinary system, skeletal system/limbs, and systemic abnormalities such as fetal hydrops, abnormally thickened placenta with hydrops, and severe growth restriction. Criteria for ultrasound soft markers and structural malformations are provided in the appendices.
- Planned to undergo at least one invasive or postnatal procedure for genetic diagnosis, and consent to the use of residual diagnostic samples for research testing.
- Signed unified informed consent form, agreement to follow-up, and consent for storage and submission of samples and data according to the protocol.
Who cannot join
- Age < 18 years or individuals lacking full capacity for civil conduct.
- Twin or multiple pregnancies.
- Known parental or familial carrier status of a pathogenic variant highly consistent with the current fetal phenotype, where testing is planned only for targeted confirmation.
- Refusal to consent to the storage and use of samples and data for this study.
- Other conditions deemed unsuitable for participation in this study by the investigator.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China4 sites, 4 recruiting
- Recruiting
Women's Hospital School of Medicine Zhejiang University
Hangzhou, Zhejiang, 310006
Qiong Luo, +86 571 89998819, luoq@zju.edu.cn
- Recruiting
Huzhou Maternity & Child Care Hospital
Huzhou, Zhejiang, 313000
Liping Qiu, +86 15906823270, 392686340@qq.com
- Recruiting
Quzhou Maternal and Child Health Care Hospital
Quzhou, Zhejiang, 324000
Yuying Zhu, +86 15257023995, zhuyuy123@163.com
- Recruiting
Shaoxing Maternity & Child Care Hospital
Shaoxing, Zhejiang, 312000
Hualin Xu, +86 13867526767, xhl0175@sina.cn
About this study
Official title: Clinical Study on Prenatal Diagnosis of Fetal Abnormalities of Unknown Cause Using Whole-Genome Sequencing: A Multicenter Study
The goal of this observational study is to learn if whole-genome sequencing (WGS) can help find the genetic cause in fetuses with structural abnormalities that remain unexplained after standard genetic testing (such as karyotyping, chromosomal microarray, or whole-exome sequencing). It will also learn how WGS results may affect pregnancy management and family decision-making.
The main questions it aims to answer are:
Read more
How often does WGS identify a genetic cause in these fetuses? Does WGS find more genetic causes compared to standard genetic tests? Can combining WGS with other molecular analyses help discover new disease genes or pathways? Researchers will compare WGS results to results from standard genetic tests to see if WGS finds more genetic causes.
Participants are pregnant women whose fetuses have structural abnormalities seen on ultrasound or MRI, with negative results from routine genetic testing. Participants will:
Undergo an invasive procedure (such as amniocentesis) or provide postnatal samples as part of their regular medical care Allow the use of leftover samples for WGS and additional molecular studies Be followed until after delivery to collect information on pregnancy outcomes and neonatal health
- Conditions
- Prenatal Diagnosis, Fetal Diseases
- Medical subject headings
- Fetal Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic yield of WGS
Proportion of fetuses with structural malformations or significant ultrasound abnormalities in whom whole-genome sequencing (WGS) using fetal and related tissues identifies at least one pathogenic or likely pathogenic variant. Overall diagnostic yield (including pathogenic/likely pathogenic variants and variants of uncertain significance reclassified as pathogenic/likely pathogenic based on additional evidence) will also be reported.
Measured: 8 weeks after enrollment of the last participant
Comparison of diagnostic increment of WGS vs. standard clinical testing pathway
Difference in diagnostic rate (proportion of fetuses with pathogenic/likely pathogenic variants) between whole-genome sequencing (WGS) and the current standard clinical testing pathway (karyotyping, CMA/CNV-seq, WES/panel). Stratified analysis by malformation type (e.g., isolated CNS, cardiac, skeletal, multiple systems) and by pattern of system involvement will be reported.
Measured: 12 weeks after enrollment of the last participant
Number of novel candidate disease genes and enriched molecular pathways
Count of novel candidate disease genes or regulatory elements identified by integrated multi-omics analysis. List of enriched KEGG pathways and GO terms (with FDR < 0.05) associated with fetal developmental abnormalities.
Measured: At study completion (average 24 months after first participant enrollment)
Secondary outcomes (4)
Phenotypic stratification system and gene pathway enrichment results
Phenotypic classification system (based on organ/system involvement: isolated, multiple, syndromic). For each subtype: (1) count and frequency of pathogenic/likely pathogenic variants; (2) count of variant types (SNV, Indel, SV, CNV); (3) list of enriched KEGG pathways and GO terms with FDR < 0.05.
Measured: At study completion (average 24 months after first participant enrollment)
Reclassification rate of variants of uncertain significance (VUS) and impact on counseling decisions
Proportion of VUS reclassified to pathogenic/likely pathogenic or benign/likely benign after multi-omics integration. Number of participants/families with altered genetic counseling or clinical decision-making (e.g., termination, prenatal intervention, postnatal follow-up plan) due to reclassification.
Measured: At study completion (average 24 months after first participant enrollment)
Establishment of a multicenter database and biobank
A unified, relational database containing de-identified clinical phenotypes, genotypes (WGS variants), multi-omics data (e.g., transcriptomic, epigenomic), and biospecimen inventory (e.g., DNA, RNA, plasma, tissue blocks) from participating centers. Database completion will be defined as ≥90% of expected participants with all required data types uploaded and quality-controlled. Biobank completion will be defined as ≥90% of expected biospecimens collected, processed, and stored with traceable metadata.
Measured: At study completion (average 24 months after first participant enrollment)
Standardized data submission and sharing protocols
Completion of a written protocol document (yes/no) covering sample submission, data formats, quality thresholds, reporting template (ACMG/AMP classification), clinical data dictionary, and de-identification rules, with sign-off obtained from all participating centers' principal investigators and data managers.
Measured: At study completion (average 24 months after first participant enrollment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2026
- Study start12 Mar 2026
- Primary completion12 Sep 2027 (estimated)
- Study completion12 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prenatal DiagnosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Women's Hospital School Of Medicine Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07606989
- Sponsor's protocol ID
- IRB-20260095-R
- Status last verified
- Mar 2026
- First submitted
- 9 Apr 2026
- Last updated
- 26 May 2026
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on Prenatal Diagnosis of Fetal Abnormalities of Unknown Cause Using Whole-Genome Sequencing: A Multicenter Study
- ClinicalTrials.gov ID
- NCT07606989
- Acronym / sponsor ID
- IRB-20260095-R
- Conditions
- Prenatal Diagnosis, Fetal Diseases
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Women's Hospital School Of Medicine Zhejiang UniversityUniversity, hospital or other
- Study start
- 12 Mar 2026 (actual)
- Primary completion
- 12 Sep 2027 (estimated)
- Study completion
- 12 Mar 2028 (estimated)
- First posted
- 26 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to learn if whole-genome sequencing (WGS) can help find the genetic cause in fetuses with structural abnormalities that remain unexplained after standard genetic testing (such as karyotyping, chromosomal microarray, or whole-exome sequencing). It will also learn how WGS results may affect pregnancy management and family decision-making.
The main questions it aims to answer are:
How often does WGS identify a genetic cause in these fetuses? Does WGS find more genetic causes compared to standard genetic tests? Can combining WGS with other molecular analyses help discover new disease genes or pathways? Researchers will compare WGS results to results from standard genetic tests to see if WGS finds more genetic causes.
Participants are pregnant women whose fetuses have structural abnormalities seen on ultrasound or MRI, with negative results from routine genetic testing. Participants will:
Undergo an invasive procedure (such as amniocentesis) or provide postnatal samples as part of their regular medical care Allow the use of leftover samples for WGS and additional molecular studies Be followed until after delivery to collect information on pregnancy outcomes and neonatal health
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant women aged 18 years or older with singleton pregnancies, whose fetuses have structural abnormalities detected by ultrasound or MRI between 11+0 and 32+0 weeks of gestation, and who are scheduled to undergo invasive or postnatal genetic diagnostic procedures.
Key inclusion criteria (5 listed)
- Pregnant women aged ≥ 18 years.
- Singleton pregnancy.
- Gestational age between 11+0 and 32+0 weeks, with ultrasound or MRI indicating a definite structural malformation in the fetus (may be with or without soft marker abnormalities) requiring prenatal diagnosis (see Appendices 1 and 2). Fetal developmental abnormalities include those of the central nervous system, cardiovascular system, craniofacial/neck region, chest/mediastinum, abdomen/digestive tract, urinary system, skeletal system/limbs, and systemic abnormalities such as fetal hydrops, abnormally thickened placenta with hydrops, and severe growth restriction. Criteria for ultrasound soft markers and structural malformations are provided in the appendices.
- Planned to undergo at least one invasive or postnatal procedure for genetic diagnosis, and consent to the use of residual diagnostic samples for research testing.
- Signed unified informed consent form, agreement to follow-up, and consent for storage and submission of samples and data according to the protocol.
Key exclusion criteria (5 listed)
- Age < 18 years or individuals lacking full capacity for civil conduct.
- Twin or multiple pregnancies.
- Known parental or familial carrier status of a pathogenic variant highly consistent with the current fetal phenotype, where testing is planned only for targeted confirmation.
- Refusal to consent to the storage and use of samples and data for this study.
- Other conditions deemed unsuitable for participation in this study by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic yield of WGS
Time frame: 8 weeks after enrollment of the last participant
Proportion of fetuses with structural malformations or significant ultrasound abnormalities in whom whole-genome sequencing (WGS) using fetal and related tissues identifies at least one pathogenic or likely pathogenic variant. Overall diagnostic yield (including pathogenic/likely pathogenic variants and variants of uncertain significance reclassified as pathogenic/likely pathogenic based on additional evidence) will also be reported.
Comparison of diagnostic increment of WGS vs. standard clinical testing pathway
Time frame: 12 weeks after enrollment of the last participant
Difference in diagnostic rate (proportion of fetuses with pathogenic/likely pathogenic variants) between whole-genome sequencing (WGS) and the current standard clinical testing pathway (karyotyping, CMA/CNV-seq, WES/panel). Stratified analysis by malformation type (e.g., isolated CNS, cardiac, skeletal, multiple systems) and by pattern of system involvement will be reported.
Number of novel candidate disease genes and enriched molecular pathways
Time frame: At study completion (average 24 months after first participant enrollment)
Count of novel candidate disease genes or regulatory elements identified by integrated multi-omics analysis. List of enriched KEGG pathways and GO terms (with FDR < 0.05) associated with fetal developmental abnormalities.
4 secondary outcomes
Phenotypic stratification system and gene pathway enrichment results
Time frame: At study completion (average 24 months after first participant enrollment)
Reclassification rate of variants of uncertain significance (VUS) and impact on counseling decisions
Time frame: At study completion (average 24 months after first participant enrollment)
Establishment of a multicenter database and biobank
Time frame: At study completion (average 24 months after first participant enrollment)
Standardized data submission and sharing protocols
Time frame: At study completion (average 24 months after first participant enrollment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prenatal Diagnosis and Fetal Diseases, run by Women's Hospital School Of Medicine Zhejiang University at 4 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Qiong Luo (+86 571 89998819, luoq@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic yield of WGS (time frame: 8 weeks after enrollment of the last participant). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.